The long-term objectives of this application are to identify the mechanisms of constrictor agonist-induced changes in pulmonary elastance and resistance. Specific aims test the following hypotheses: During agonist induces-constriction, changes in dynamic lung elastance (Edyn,L) and tissue resistance (Rti) are determined in part by, 1) nonhomogeneity of lung expansion, and 2) increases of axial elastic stresses in the bronchial wall. Hypothesis #1 will be examined by simultaneously measuring regional lung volumes (Vr,i) and regional alveolar pressures (PA,i) under various experimental conditions, before and during induces constriction. Vr,i and PA,i will be determined with the parenchymal marker technique and the alveolar capsule technique, respectively. Regional Rti and Edyn, L will be derived form Vr,i and PA,i. Hypothesis #2 will be tested by comparing length-transpulmonary pressure relationships of bronchial segments in situ with length-axial tension relationships of excised bronchi during different static and dynamic loads. The proposed research will shed light on mechanisms of lung constriction and mechanical interdependence between the airways and lung parenchyma. The candidate is an international graduate, who is currently on the faculty of Baylor College of medicine with the academic rank of Assistant Professor of Pediatrics. He has been involved in basic research since 1987, with a recess from 1992 to 1995 during which he did a residency training in Pediatrics and served in a Health Professional Shortage area. He has a strong desire to further develop the essential research skills necessary for a productive academic career. It is hoped that the experience and training gained during the duration of this grant will allow Dr. Shardonofsky to become an independent investigator eligible for further NIH funding. Dr. Joe Rodarte is Professor of Medicine and Chief, Pulmonary and Critical Care Section at Baylor College of Medicine, and Adjunct Professor of Mechanical Engineering at Rice University. Through bench research under the supervision of Dr. Rodarte, and independent study program which covers most of the topics relevant to the candidate's scientific development, and regular attendance to research symposiums held at the Bioengineering Department of Rice University, Dr. Shardonofsky will have the opportunity to mature as a basic science investigator in a structured project.